Alcohol is among the most widely abused drugs in the world, yet our understanding of the mechanisms by which it regulates brain function and behavior remain largely unclear. This proposal describes the identification of a mutation (P-16-99) in a Drosophila Discs Large (Dig) gene, which causes an altered behavioral response to ethanol. The goal of this project is to use PI 6-99 to investigate the role of Dig in the development of ethanol tolerance. The specific aims are: [unreadable] Aim #1: To obtain phenotypic rescue of the tolerance defect of the PI6-99 strain using transgenic flies expressing the dig gene and to define the precise molecular lesion induced by the PI6-99 mutation. [unreadable] Aim #2. To determine the temporal requirements for dig function during ethanol tolerance development. [unreadable] Aim #3. To define the structural domains of Dig that play roles in ethanol tolerance development. [unreadable] Aim #4: To study the role of known Dig-interacting proteins, such as the NMDA receptor and CaM Kinase II in ethanol tolerance. [unreadable] [unreadable]